Various ailments may lead to high phosphate concentrations in the blood in animals, particularly warm-blooded animals such as humans. This can lead to a number of physiological problems, such as deposition of calcium phosphate.
In patients with kidney failure who are being treated by regular haemodialysis, phosphate concentrations in the blood plasma can rise dramatically and this condition, known as hyperphosphataemia, can result in calcium phosphate deposition in soft tissue. Plasma phosphate levels may be reduced by oral intake of inorganic and organic phosphate binders.
Classes of inorganic solid phosphate binders are disclosed in WO 99/15189. These include alkali treated inorganic sulphates, such as calcium sulphate, and mixed metal compounds which are substantially free from aluminium and which have a phosphate binding capacity of at least 30% by weight of the total weight of phosphate present, over a pH range of from 2-8, as measured by the phosphate binding test as described therein. The inorganic solids are water insoluble and are primarily intended for oral administration.
Typically such mixed metal compounds may contain iron (III) and at least one of magnesium, calcium, lanthanum and cerium. Preferably they also contain at least one of hydroxyl and carbonate anions and optionally additionally, at least one of sulphate, chloride and oxide.
Mixed metal compounds such as described in WO 99/15189 present particular problems in the formulation of unit dosages containing them. In part, these problems arise from the fact that the compounds need to be dosed in relatively large amounts. This means that in order for a unit dose to be of a size which does not make it too difficult to swallow, assisting with patient compliance, the inclusion level of the active ingredient needs to be quite high, leaving very little formulation space for excipients.
There is a need for unit doses containing such inorganic solid phosphate binders which include high levels of the pharmaceutically active ingredient yet which maintain physical integrity and stability on storage. There is also a need for such unit doses to disintegrate in order to release the solid inorganic phosphate binder in the stomach and to give rapid phosphate binding, but not to disintegrate excessively in the mouth or oesophagus resulting in an unpleasant taste and potential lack of patient compliance. There is also a need for processing routes for forming the solid inorganic phosphate binders into unit doses without problems caused by poor flowability of the material and yet without excessive hindering of the rate of phosphate binding for the material.